Objective: To investigate the effect of injection combined with fluoxetine in the treatment of senile dementia with depression. Methods: Ninety cases of senile dementia complicated with depression were selected from January 2014 to September 2015 in The First Hospital Affiliated to Guangdong Pharmaceutical University. The patients were divided into the study group and the control group by the random number table method. Patients in the study group were treated with combination therapy of injection and fluoxetine, and the control group was treated with fluoxetine only. We evaluated the depression and quality of life when the patients were admitted to the hospital and leave hospital by Hamilton Depression Scale (HAMD), disease self-management efficiency measuring table and the WHO quality of life scale (QOL-BREF). Compared the incidence of adverse reactions and Unified Parkinson’s Disease Rating Scale (UPDRS) in the two groups before and after the treatment. Results: HAMD, QOL-BREF scores were high in all patients on admission to hospital and have no statistical difference (P>0.05); when discharged from hospital, HAMD, QOL-BREF scores of the study group and the control group of patients declined in different degree, but data between the groups have significant difference (P<0.05); before treatment, there was no significant difference in the UPDRS score between the two groups (P>0.05), after treatment the UPDRS score of the study group was significantly lower than that in the control group (P<0.05); there was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Thorn slender acanthopanax injection combined with fluoxetine has good remission and effect in treatment of senile dementia, and their combination has a good clinical significance for the quality of life of elderly patients with dementia.